Apparatus for execution of treatment operations in connection with colouring of tissue specimens on object glasses

ABSTRACT

An apparatus for automatic execution of different treatment operations in connection with staining of tissue specimens on microscope slides, wherein the apparatus ( 1 ) comprises a loading station ( 2 ) for microscope slides ( 7 ) with tissue specimens, a number of reagent stations ( 3 ) for staining of the tissue specimens on supplied microscope slides, a conveyor ( 5 ) for transfer of microscope slides ( 7 ) between the stations ( 3 ) in accordance with a staining program, an unloading station ( 10 ) for treated microscope slides, and a control unit ( 19 ) for controlling the treatment operations in accordance with a data program. The apparatus comprise a photo station ( 25 ) with a digital camera ( 26 ) for automatic photographing with a background light source of the finished treated tissue specimens on supplied microscope slides ( 7 ). The camera is connected to the control unit ( 19 ) of the apparatus and the control unit is arranged to store the picture of each individual tissue specimen and information which is located on the relevant microscopic slide ( 7 ) and preferably also information about the staining program and status of reagents at the reagent stations ( 3 ) for automatic transmission of the information to a place for result analysis.

This is a 371 filing of International Patent Application No.PCT/NO2007/000031 filed Jan. 31, 2007 and published on Aug. 9, 2007under publication number WO 2007/089155 A and claims priority benefitsfrom Norwegian Patent Application No. 20060555 filed Feb. 2, 2006, thedisclosure of which is hereby incorporated by reference.

The invention relates to an apparatus for automatic execution ofdifferent treatment operations in connection with staining of tissuespecimens on microscope slides, wherein the apparatus comprises aloading station for microscope slides with tissue specimens, a number ofreagent stations for staining of the tissue specimens on suppliedmicroscope slides, a conveyor for transfer of microscope slides betweenthe stations in accordance with a staining program, an unloading stationfor treated microscope slides, and a control unit for controlling thetreatment operations in accordance with a data program.

An apparatus of the above-mentioned type is shown and described inNorwegian patent application No. 2004 5622. With such an apparatus manydifferent treatment operations can be executed, such as initial fixingof paraffin casted tissue specimens on microscope slides, staining oftissue specimens on microscope slides, mounting of cover glasses on thestained tissue specimens microscope slides, and drying of stained tissuespecimens microscope slides after application of glue and mounting ofcover glasses, in accordance with a selected programmed running process.

After the current treatment operations of the said type have beenexecuted, the microscope slides are according to usual practice todaysubjected to manual micro-scoping. This treatment comprises also manualloading of photo equipment for taking pictures of the tissue specimenswith a view to result analysis (so-called “screening”). By the manualmicroscoping, it must be waited 24 hours after the application of thecover glasses so that the specimens no longer liberate much dissolventgasses. Additionally that the manual handling is comparatively timeconsuming it may also be exposed to human error, e.g. due to erroneousregistration or mixed up patient data.

A main object of the invention is to provide an apparatus of the currenttype, which is able to store all information about each specimen withoutany source of error, in such a way that a 100% quality assurance of thespecimen results is obtained.

An additional object of the invention is to provide an apparatus, whichmakes it possible, that the specimens can be studied essential fasterthan with manual micro-scoping, which means an essential labour savingfor a user.

The above-mentioned objects are achieved by means of an apparatus of theintroductorily stated type, which, according to the invention, ischaracterised in that the apparatus comprise a photo station with adigital camera for automatic photographing with a background lightsource of the finished treated tissue specimens on supplied microscopeslides, the camera is connected to the control unit of the apparatus andthe control unit is arranged to store the picture of each individualtissue specimen and information which is located on the relevantmicroscopic slide and preferably also information about the stainingprogram and status of reagents at the reagent stations for automatictransmission of the information to a place for result analysis.

Preferable embodiments are stated in the dependent claims.

The invention will now be further described by means of an exemplaryembodiment with reference to the drawings, wherein

FIG. 1 shows a schematic side view of an apparatus according to theinvention, and

FIG. 2 shows a plan view of a carrier device for microscope slides foruse in the apparatus shown in FIG. 1.

In FIG. 1 it is shown an apparatus corresponding to the apparatus whichis shown and described in the previously mentioned Norwegian patentapplication No 2004 5622 which additionally is provided with a photostation according to the present invention. In the following a briefdescription of the structure of the apparatus shall be given. For afurther description of the apparatus and its manner of operation,reference is made to the said patent application.

The apparatus 1 shown in the drawing comprises three levels I, II andIII, having units for execution of the relevant treatment operations.

The first level I includes a loading and preheating station 2 formicroscope slides, a number of reagent stations 3 consisting of vessels4 with reagents for staining of tissue specimens on microscope slides,and a conveyor 5 for transfer of carriers/holding devices 6 withmicroscope slides 7, (see FIG. 2) from vessel to vessel in accordancewith a selected staining/data program.

The second level II includes a station 8 for application of coverglasses (not shown) on the stained microscope slides, a succeedingdrying station 9 and a storing/unloading station 10 for theready-treated microscope slides. In the illustrated embodiment, thesecond level II is located above the first level I, and a hoist orlifting means 11 is provided for transfer of carriers 6 with stainedmicroscope slides from the first level to the cover glass applyingstation 8 on the second level. A horizontal transport means 12 isprovided for transfer of carriers 6 with microscope slides 7 through thecover glass applying station 8 and the drying station 9 to the unloadingstation 10.

The third level III, which is located below the first level 1, includesan assembly 13 of a number of storage tanks 14 for the relevant reagentliquids, wherein the tanks are connected to the appurtenant vessel 4 atthe reagent stations 3 via connecting lines (not shown) on which thereare arranged pumps 15 for the supply of liquid to the vessels, andmoreover filers 16 for filtering of the liquids.

The apparatus is also shown to include a filter/blower unit 17 forventilation of the apparatus. This unit is in communication with a ventinlet 18 at the top of the apparatus, and thereby provides for transportand blowout of venting air through the apparatus. In this manner, thewhole apparatus is ventilated, so that i.a. dangerous fumes from thereagent stations are removed in a justifiable manner.

The apparatus also includes an electronic control unit which issymbolically shown as a block 19, and which takes care of controllingthe treatment operation of the apparatus in accordance with a dataprogram. Further, the apparatus comprises a control panel (not shown)for operation and working of the apparatus. This panel includes a numberof touch or contact keys (control keys and working keys), and also adisplay giving information about the status etc. of the apparatus duringthe operation.

The means 11 for gripping and transfer of carriers is only schematicallyshown in FIG. 1, and consists of a hoist for lifting of the carriers inthe dedicated transfer area 20 to the second level II. As an alternativeto such a lifting means, the transfer means may be arranged at thesecond level and arranged to fetch carriers 6 from the area 20 to thesecond level.

The station 8 for application of cover glasses on the stained microscopeslides is also only schematically shown in FIG. 1. This station includesa number of elements, more specifically a cover glass magazine with adispenser function, a glue pump, a glue dispenser and a unit formounting of cover glasses on the supplied microscope slides with stainedtissue specimens. Further, the station contains a detection unit fordetection of microscope slides arriving at the station in the differentsupplied carriers. The cover glass magazine advantageously may beconstructed for delivering cover glasses laterally from the bottom ofthe magazine. For a further description of such a station reference maye.g. be made to the international patent application No. PCT/NO99/00396(WO 00/37986).

For a further description of the carrier device/carrier 6 reference ismade to the previously mentioned Norwegian patent application and alsothe Norwegian patent application 2004 5625.

In accordance with the invention the above-described apparatus isprovided with a photo station 25 on which it is arranged a digitalcamera for automatic photographing with a background light source of thefinished treated and sealed tissue specimens on the supplied microscopeslides 7. The camera is in a known way connected to the control unit 19of the apparatus and the control unit is arranged to store the pictureof each individual tissue specimen and information which is located onthe relevant microscope slide and possibly also information about thecurrent staining program and status of reagents at the reagents stations3 for automatic transmission of the information to a place for resultanalysis.

As shown, the photo station 25 is arranged after the station 8 forapplication of cover glasses on the tissue specimens on the microscopeslides, wherein the applying station is arranged to receive successivecarriers 6 that are taking up a number of microscope slides 7 locatedside by side in a common plane as shown in FIG. 2. As shown, the carrier6 in FIG. 2 is dimensioned to take up ten microscope slides.

The digital camera 26 may possibly be mounted on a microscope for makingenlarged photos if the tissue specimens, or the camera may be of a type,which is especially suitable for this purpose.

The camera and the carriers 6 with the microscope slides 7 are arrangedto carry out a mutual movement for location of the camera oversuccessive microscope slides or over successive parts of a microscopeslide. Thus, the camera unit may be moved over a microscope slide fortaking the necessary number of pictures, or the microscope slide may bemoved under the camera unit for taking the necessary number of pictures,or a combination of movements of the camera unit and the currentmicroscope slide may be used. Generally, the camera then will be mountedon a step-by-step movable unit.

In a suitable embodiment, the movable unit may be arranged to be movedlaterally in a y-direction only. In a further embodiment the apparatuscomprises a transport belt for step by step movement in a x-direction ofgroups of microscope slides which are located side by side (in they-direction) on the transport belt. In a supposition that it in thisembodiment is needed four pictures of each microscope slide, firstly theidentification field on the microscope slides in the current group willbe photographed, after which the transport belt is moved approx. ¼ ofthe length of the microscope slide, and the camera unit is moved backfor executing the same operation until the whole microscope slide andall microscope slides of the group are photographed. Then the softwareof the apparatus will put together the four pictures of each microscopeslide tissue specimen and the identification—or information field.

The picture or pictures of the tissue specimen on microscope slides, allinformation on the belonging label on the microscope slide and alsoinformation about which staining program this microscope slide has gonethrough and status of the reagents can automatically be stored in themicroprocessor which is included in the control unit of the apparatus,or possibly in a connected server. Thus, this information canautomatically be loaded and without unnecessary time delay to the placewhere the result analysis (the screening) is carried out. Thus, thespecimen can be analysed on a display by a pathologist. The pathologistmay e.g. be localized in another building or another place in the world,and the picture information can be transmitted via e.g. the Internet. Bypossible problems with the reading etc., a local pathologist may in anycase receive the tissue specimen slide for an ordinary screening undermicroscope. Today it also exists software which helps the pathologistsby localizing “problem areas” in a tissue specimen and which may presenta preliminary diagnosis. It is likely that this technology will beconsiderably better and faster in the future.

A photo station of the above-mentioned type can be used on conventionalstaining machines and on so called immune staining machines where acover glass or a film is placed on the tissue specimen slide so that apicture can be taken.

1. An automated stainer comprising multiple stations for automaticexecution of different operations in connection with staining of tissuespecimens on microscope slides, the multiple stations comprising: aloading station configured to load the microscope slides on theapparatus; two or more staining stations configured to stain the tissuespecimens on the microscope slides; a cover-glass application stationconfigured to automatically mount cover glasses on the stained tissuespecimens on the microscope slides; and a photo station comprising acamera mounted on a microscope, wherein the photo station is fitted witha background light source to take one or more back lit photomicrographsof the stained tissue specimens on the microscope slides.
 2. Anapparatus according to claim 1, further comprising a conveyor fortransporting the microscope slides between the two or more treatmentstations.
 3. An apparatus according to claim 1, wherein the photostation is mounted on a step by step movable unit for positioning themicroscope over successive microscope slides, or over successive partsof a microscope slide.
 4. An apparatus according to claim 3, wherein themovable unit is arranged to be moved only laterally in a y-direction,the apparatus further comprising a transport belt for step by stepmovement in a x-direction of groups of microscope slides which arelocated side by side (in the y-direction) on the transport belt.
 5. Anapparatus according to claim 1, further comprising a control unit havinga microprocessor configured to control the execution of the differenttreatment operations.
 6. An apparatus according to claim 5, wherein thecontrol unit is configured to store the micrographs of the stainedtissue specimen.
 7. An apparatus according to claim 5, wherein thecontrol unit is configured to transmit the micrographs of the stainedtissue specimen to a remote analysis unit for further processing.
 8. Anapparatus according to claim 1, further comprising one or more reagentstorage tanks connected to the reagent vessels in the two or moretreatment stations.